WO2012057101A1 - マイクロチップ、マイクロチップの成形型、及びマイクロチップを製造する製造装置 - Google Patents
マイクロチップ、マイクロチップの成形型、及びマイクロチップを製造する製造装置 Download PDFInfo
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- WO2012057101A1 WO2012057101A1 PCT/JP2011/074478 JP2011074478W WO2012057101A1 WO 2012057101 A1 WO2012057101 A1 WO 2012057101A1 JP 2011074478 W JP2011074478 W JP 2011074478W WO 2012057101 A1 WO2012057101 A1 WO 2012057101A1
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- Prior art keywords
- microchip
- mold
- substrate
- protrusion
- diameter
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Classifications
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C45/00—Injection moulding, i.e. forcing the required volume of moulding material through a nozzle into a closed mould; Apparatus therefor
- B29C45/17—Component parts, details or accessories; Auxiliary operations
- B29C45/26—Moulds
- B29C45/263—Moulds with mould wall parts provided with fine grooves or impressions, e.g. for record discs
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502707—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C45/00—Injection moulding, i.e. forcing the required volume of moulding material through a nozzle into a closed mould; Apparatus therefor
- B29C45/17—Component parts, details or accessories; Auxiliary operations
- B29C45/26—Moulds
- B29C45/2628—Moulds with mould parts forming holes in or through the moulded article, e.g. for bearing cages
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B32—LAYERED PRODUCTS
- B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
- B32B3/00—Layered products comprising a layer with external or internal discontinuities or unevennesses, or a layer of non-planar shape; Layered products comprising a layer having particular features of form
- B32B3/26—Layered products comprising a layer with external or internal discontinuities or unevennesses, or a layer of non-planar shape; Layered products comprising a layer having particular features of form characterised by a particular shape of the outline of the cross-section of a continuous layer; characterised by a layer with cavities or internal voids ; characterised by an apertured layer
- B32B3/266—Layered products comprising a layer with external or internal discontinuities or unevennesses, or a layer of non-planar shape; Layered products comprising a layer having particular features of form characterised by a particular shape of the outline of the cross-section of a continuous layer; characterised by a layer with cavities or internal voids ; characterised by an apertured layer characterised by an apertured layer, the apertures going through the whole thickness of the layer, e.g. expanded metal, perforated layer, slit layer regular cells B32B3/12
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B32—LAYERED PRODUCTS
- B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
- B32B3/00—Layered products comprising a layer with external or internal discontinuities or unevennesses, or a layer of non-planar shape; Layered products comprising a layer having particular features of form
- B32B3/26—Layered products comprising a layer with external or internal discontinuities or unevennesses, or a layer of non-planar shape; Layered products comprising a layer having particular features of form characterised by a particular shape of the outline of the cross-section of a continuous layer; characterised by a layer with cavities or internal voids ; characterised by an apertured layer
- B32B3/30—Layered products comprising a layer with external or internal discontinuities or unevennesses, or a layer of non-planar shape; Layered products comprising a layer having particular features of form characterised by a particular shape of the outline of the cross-section of a continuous layer; characterised by a layer with cavities or internal voids ; characterised by an apertured layer characterised by a layer formed with recesses or projections, e.g. hollows, grooves, protuberances, ribs
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0809—Geometry, shape and general structure rectangular shaped
- B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/24—Structurally defined web or sheet [e.g., overall dimension, etc.]
- Y10T428/24273—Structurally defined web or sheet [e.g., overall dimension, etc.] including aperture
- Y10T428/24322—Composite web or sheet
- Y10T428/24331—Composite web or sheet including nonapertured component
Definitions
- the present invention relates to a microchip, a mold, and a microchip manufacturing apparatus.
- a micro-channel that uses microfabrication technology to form fine channels and circuits on a silicon or glass substrate to perform chemical reactions, separation, and analysis of a liquid sample such as nucleic acid, protein, or blood in a minute space
- a device called a chip also referred to as a micro analysis chip or a microfluidic chip
- ⁇ TAS Micro Total Analysis Systems
- a microchip also referred to as a microfluidic chip
- the amount of sample and reagent used or the amount of waste liquid discharged can be reduced, and an inexpensive system that can be carried in a small space can be realized.
- a microchip is manufactured by bonding two members that have been finely processed to at least one member.
- resin-made macro chips have been proposed for easy and low-cost manufacturing. More specifically, in order to manufacture a resin microchip, a resin substrate having a channel groove on the surface and a resin cover member (for example, a film) covering the channel groove are provided. Join. In the substrate having the channel groove, a through-hole penetrating in the thickness direction is formed at the end of the channel groove or the like. Then, the substrate having the channel groove on the surface and the cover member are joined with the channel groove inside. By this joining, the cover member functions as a lid for the channel groove, and the channel is formed by the channel groove and the cover member. Thereby, the microchip which has a flow path inside is manufactured. Further, the flow path and the outside of the microchip are connected by a through hole formed in the substrate, and a liquid sample is introduced and discharged through the through hole.
- the present invention has been made in view of the circumstances as described above, and it is possible to determine the position of the observation channel, and to improve the degree of design freedom, a microchip molding die, and An object of the present invention is to provide a microchip manufacturing apparatus.
- a mold for molding a substrate provided in a microchip The substrate is A channel groove is formed on one surface, and a positioning reference hole for the groove is formed in the thickness direction from the one surface.
- a cover member is bonded to the one surface to form the microchip,
- the mold is The first type;
- a second mold provided so as to be able to contact and separate from the first mold, Of the first mold and the second mold, one mold for molding the one surface is A ridge for forming the groove; It has a column-shaped 1st projection part which shape
- a microchip manufacturing apparatus for manufacturing a microchip in which a substrate and a cover member are bonded together
- the substrate is A channel groove is formed on one surface, and a positioning reference hole for the groove is formed through the thickness direction, As a mold for the substrate, It is provided with the shaping
- the substrate is By being formed by molding, A channel groove is formed on one surface, and a positioning reference hole for the groove is formed through the thickness direction, The hole is A first recess recessed from the one surface of the substrate toward the other surface; A second recessed portion recessed from the other surface toward the one surface is formed in communication; The second recess has an inner diameter larger than that of the first recess.
- the substrate has a channel groove formed on one surface, and a positioning reference hole for the groove is formed in the thickness direction from the one surface.
- one mold for molding one surface to which the cover member is bonded is provided with a protrusion that molds a groove and at least the inner diameter of at least the hole. Since the columnar first protrusion for forming the minimum diameter portion is provided, the minimum diameter portion of the hole, that is, the portion specified as the position of the hole, and the channel groove are formed by the same mold.
- the Rukoto is provided in one of the first mold and the second mold.
- the positional relationship between the channel groove and the minimum diameter portion of the hole can be kept constant between molding shots, so the position of the observation channel is determined based on the position of the minimum diameter portion of the hole. Accurately determined. Therefore, since there is no need to provide a conventional positioning channel, the position of the observation channel can be determined and the degree of freedom in design can be improved. In addition, since it is possible to save the trouble of performing the processing for determining the position of the observation channel such as focusing at every measurement, the control during the use of the microchip can be simplified and the inspection time can be shortened. .
- the substrate is formed by molding, so that a channel groove is formed on one surface bonded to the cover member, and a positioning reference for the groove is provided.
- a first recess formed in the substrate so as to be recessed from the one surface to the other surface, and from the other surface toward the one surface. Since the hole is formed by communicating with the recessed second recessed portion, the channel groove and the first recessed portion are one of the first mold and the second mold when forming the substrate. It is formed by the same mold. Further, since the second recess has an inner diameter larger than that of the first recess, the minimum diameter portion of the hole is present in the first recess.
- the minimum diameter of the hole portion is Based on the position of the portion, the position of the observation channel can be accurately determined. Therefore, since there is no need to provide a conventional positioning channel, the position of the observation channel can be determined and the degree of freedom in design can be improved. In addition, since it is possible to save the trouble of performing the processing for determining the position of the observation channel such as focusing at every measurement, the control during the use of the microchip can be simplified and the inspection time can be shortened. .
- FIG. 1 is a perspective view illustrating an example of an external configuration of the inspection apparatus 1
- FIG. 2 is a schematic diagram illustrating an example of an internal configuration of the inspection apparatus 1.
- the inspection apparatus 1 includes a tray 10 on which the microchip 2 is placed, a transport port 11 into which the microchip 2 is carried from the tray 10 by a loading mechanism (not shown), and details of inspection and inspection.
- An operation unit 12 for inputting target data and the like, a display unit 13 for displaying inspection results, and the like are provided.
- the inspection apparatus 1 includes a liquid feeding unit 14, a heating unit 15, a voltage application unit 18, a detection unit 16, a drive control unit 17, and the like.
- the liquid feeding unit 14 is a unit for feeding the liquid in the microchip 2 and is connected to the microchip 2 carried into the inspection apparatus 1 from the carrying port 11.
- the liquid feeding unit 14 includes a micropump 140, a chip connection unit 141, a driving liquid tank 142, a driving liquid supply unit 143, and the like.
- one or more micropumps 140 are provided in the liquid feeding unit 14, and the driving liquid 146 is injected into the microchip 2 or a fluid such as an analysis sample is sucked from the microchip 2. Then, liquid feeding in the microchip 2 is performed.
- each micropump 140 can be driven independently or in conjunction with each other.
- a micropump may be used only for the introduction of reagents and specimens.
- the chip connection part 141 connects the micropump 140 and the microchip 2 to communicate with each other.
- the driving liquid tank 142 stores the driving liquid 146 and supplies it to the driving liquid supply unit 143.
- the drive liquid tank 142 can be removed from the drive liquid supply unit 143 and replaced for replenishment of the drive liquid 146.
- the driving liquid supply unit 143 supplies the driving liquid 146 from the driving liquid tank 142 to the micro pump 140.
- the microchip 2 and the micropump 140 are connected and communicated by the chip connecting part 141.
- the driving liquid 146 is injected into the microchip 2 via the chip connection part 141 or is sucked from the microchip 2.
- specimens, reagents, and the like stored in the plurality of storage units in the microchip 2 are sent in the microchip 2 by the driving liquid 146.
- the specimen and reagent in the microchip 2 are mixed and reacted, and as a result, inspections such as detection of a target substance and determination of disease are performed.
- the heating unit 15 generates heat to heat the microchip 2 to a plurality of specific temperatures.
- the microchip 2 is heated to three temperatures: a heat denaturation temperature of about 95 ° C., an annealing temperature of about 55 ° C., and a polymerization temperature of about 70 ° C. Thereby, gene amplification by PCR method is performed.
- the heating unit 15 includes an element that can be increased in temperature by energization such as a heater and a Peltier element, an element that can be decreased in temperature by passing water, and the like.
- the voltage application unit 18 has a plurality of electrodes. These electrodes are inserted into the liquid sample in the microchip 2 and directly apply a voltage to the liquid sample, or contact the energizing unit 40 described later and apply a voltage to the liquid sample via the energizing unit 40. As a result, electrophoresis is performed on the liquid sample in the microchip 2.
- the detection unit 16 includes a light source such as a light emitting diode (LED) or a laser and a light receiving unit such as a photodiode (PD), and the like, and a target substance contained in a product liquid obtained by a reaction in the microchip 2 is obtained.
- Optical detection is performed at a predetermined position (a detection area 200 described later) on the microchip 2.
- the arrangement of the light source and the light receiving unit includes a transmission type and a reflection type, and may be determined as necessary.
- the drive control unit 17 includes a microcomputer, a memory, and the like (not shown), and drives, controls, and detects each unit in the inspection apparatus 1.
- FIGS. 3A, 3B, and 3C are views showing the microchip 2.
- FIG. 3A is a plan view
- FIGS. 3B and 3C are perspective views showing the internal shape as viewed from the side.
- the microchip 2 includes a substrate 3 and a film 4 bonded to each other.
- the substrate 3 has a channel groove 30 on the bonding surface to the film 4 (hereinafter referred to as the inner side surface 3A).
- the channel groove 30 forms the fine channel 20 in cooperation with the film 4 when the substrate 3 and the film 4 are bonded together.
- a detection region 200 is provided as a target substance detection target region by the detection unit 16 of the inspection apparatus 1.
- the shape of the fine channel 20 (the channel groove 30) is such that the amount of analysis sample and reagent used can be reduced, and the width, depth, etc. can be taken into consideration, such as the fabrication accuracy of molds, transferability, and releasability.
- the value is preferably in the range of 10 ⁇ m to 200 ⁇ m, but is not particularly limited.
- the width and depth of the fine channel 20 may be determined according to the use of the microchip.
- the cross-sectional shape of the fine channel 20 may be rectangular or curved.
- the substrate 3 has a plurality of through holes 31 penetrating in the thickness direction. These through-holes 31 are formed at end portions or midway portions of the flow channel groove 30, and connect the fine flow channel 20 and the outside of the microchip 2 when the substrate 3 and the film 4 are bonded together. Opening 21 to be formed is formed. This opening 21 is connected to a chip connecting part 141 (tube or nozzle) provided in the liquid feeding part 14 of the inspection apparatus 1 to introduce a gel, a liquid sample, a buffer solution or the like into the fine flow path 20, Or discharged from the fine flow path 20. In addition, an electrode (not shown) of the voltage application unit 18 in the inspection apparatus 1 can be inserted into the opening 21.
- a chip connecting part 141 tube or nozzle
- the shape of the opening 21 may be various shapes other than a circular shape and a rectangular shape. Further, for example, as shown in FIG. 3C, the periphery of the through hole 31 is projected in a cylindrical shape on the surface opposite to the inner surface 3A (hereinafter referred to as the outer surface 3B) of the substrate 3 to connect the chip connecting portion 141. It may be easy to do.
- the substrate 3 has at least one positioning hole 32 serving as a positioning reference with respect to the detection region 200 of the flow path groove 30, and in this embodiment, two.
- the positioning hole 32 is for fixing the position of the microchip 2 and thus the position of the detection region 200 to a predetermined position by inserting a fixing pin (not shown) provided in the inspection apparatus 1. 3 are provided penetrating in the thickness direction at two corner portions.
- the positioning hole 32 has a first recess 32A that is recessed from the inner surface 3A toward the outer surface 3B of the substrate 3, and the outer surface 3B toward the inner surface 3A.
- the second recessed portion 32B is formed in communication with the second recessed portion 32B.
- the first recess 32A is formed with a constant inner diameter in the thickness direction of the substrate 3, and in the present embodiment, the inner diameter is 2.0 mm.
- the first recess 32A forms a minimum diameter portion 32C of the positioning hole 32, and is thereby specified as the position of the positioning hole 32.
- the depth of the first recess 32A is 18 ⁇ m or more and 0.5 mm or less.
- a columnar projection (molded portion 606B described later) for molding the second recess 32B and a molding for molding the inner surface 3A.
- the molten resin becomes difficult to be filled between the surfaces (fixed mold-molding surface 605 described later), and the minimum diameter is not stable. If the depth is larger than 0.5 mm, the mold release property after molding is lowered, and the substrate 3 is distorted and deformed.
- the inner diameter of the second recess 32B is larger than that of the first recess 32A.
- the inner diameter of the second recess 32B is larger than that of the first recess 32A.
- the inner diameter of the tip of the second recess 32B (end on the inner surface 3A side) is the tip of the first recess 32A (outer surface). It means that it is larger than the inner diameter of the end portion on the 3B side.
- the first recess 32A has a constant inner diameter in the thickness direction of the substrate 3, and the second recess 32B is closer to the tip side.
- the taper is formed so as to reduce the inner diameter
- both the first concave portion 32A and the second concave portion 32B may be tapered in consideration of release properties after molding.
- the cross-sectional shape of the positioning hole 32 is preferably circular. It may be a polygon such as a triangle.
- one positioning hole portion 32 has the other positioning hole portion 32 in the cross section perpendicular to the thickness direction of the substrate 3 (the depth direction of the positioning hole portion 32). It is preferable that the diameter in the circumferential direction as the center is smaller than the diameter in the intersecting direction of the circumferential direction and equal to the diameter of the other positioning hole portion 32. More preferably, one positioning hole portion 32 has an inner diameter in the direction adjacent to the other positioning hole portion 32 (left-right direction in FIG. 3A) than an inner diameter in a direction orthogonal to the adjacent direction (vertical direction in the drawing). It is formed to be large. In this case, when fixing the position of the microchip 2 by fitting two fixing pins with fixed intervals into the positioning hole 32, the positioning accuracy is maintained, but the fixing to the positioning hole 32 is performed. The pin fitting operation can be facilitated.
- the film 4 is a cover member in the present invention, and in the present embodiment, is in the form of a sheet.
- the film 4 may be provided with fine flow paths and holes, it is preferable that the film 4 is not too thick in order to ensure bonding with the substrate 3.
- the electrode of the voltage application unit 18 is inserted into the opening 21 (through hole 31) and a voltage is applied to the sample in the microchannel 20 for electrophoresis. To do.
- FIGS. 5A, 5B, 6A, and 6B are perspective views showing an internal shape of a portion surrounded by a thick line in FIG. 5A and FIG. 6A.
- the conductive energizing portion 40 extends from the position facing the through hole 31 to the edge of the film 4 in the surface facing the substrate 3 in the film 4. Is provided.
- the energization unit 40 may be patterned on the film 4 by printing or the like.
- a voltage is applied to the fluid in the microchannel 20 from the edge of the film 4 via the energization unit 40 without inserting an electrode into the through hole 31 (opening 21).
- a liquid sample adheres to the electrodes and is mixed into the next microchip 2. Can be prevented.
- the electricity supply part 40 is provided in the microchip 2 of FIG. 6A, FIG. 6B, and FIG. 6C. It is provided across the opposing position of two adjacent through holes 31.
- a liquid sample or the like is supplied / discharged using the through hole 31 (opening 21) at the end of the channel groove 30 (see the arrow symbol on the left side in FIG. 6B).
- a voltage can be applied to the fluid in the microchannel 20 from the adjacent through-hole 31 (opening 21) via the energization unit 40 (see the arrow symbol on the right side in FIG. 6B), so that a plurality of Even when the microchips 2 are sequentially used, it is possible to prevent the liquid sample from adhering to the electrodes and mixing into the next microchip 2.
- the periphery of the through-hole 31 protrudes in a cylindrical shape so that the chip connecting portion 141 can be easily connected. good.
- the outer shape of the substrate 3 and the film 4 may be any shape that can be easily handled and analyzed, and is preferably a square or a rectangle in plan view.
- the size may be 10 mm square to 200 mm square. Further, the size may be 10 mm square to 100 mm square.
- the thickness of the substrate 3 having the channel groove 30 is preferably 0.2 mm to 5 mm, more preferably 0.5 mm to 2 mm in consideration of moldability.
- the thickness of the film 4 functioning as a lid (cover member) for covering the channel groove is preferably 30 ⁇ m to 300 ⁇ m, and more preferably 50 ⁇ m to 150 ⁇ m.
- the substrate 3 and the film 4 are made of resin.
- resin used for the substrate 3 and the film 4 conditions such as good moldability (transferability and releasability), high transparency, and low autofluorescence with respect to ultraviolet rays and visible light can be mentioned as conditions.
- a thermoplastic resin is used for the substrate 3 and the film 4.
- the thermoplastic resin include polycarbonate, polymethyl methacrylate, polystyrene, polyacrylonitrile, polyvinyl chloride, polyethylene terephthalate, nylon 6, nylon 66, polyvinyl acetate, polyvinylidene chloride, polypropylene, polyisoprene, polyethylene, polydimethyl.
- siloxane cyclic polyolefin or the like. Particular preference is given to using polycarbonate, polymethyl methacrylate, cyclic polyolefin.
- the same material may be used by the board
- the substrate 3 and the film 4 are made of the same type of material, they are compatible with each other, so that they are easily bonded after being melted.
- the substrate 3 and the film 4 are joined by heat fusion.
- it joins by heating the board
- a hot press machine the substrate 3 and the film 4 are sandwiched by a heated hot plate, the pressure is applied by the hot plate and held for a predetermined time, thereby bonding the substrate 3 and the film 4.
- the film 4 functions as a lid (cover member) for the flow channel groove 30, and the micro flow channel 20 is formed by the flow channel groove 30 and the film 4, whereby the microchip 2 is manufactured.
- it is only necessary to heat the interface between the substrate 3 and the film 4, and there is a possibility that only the interface can be heated by using ultrasonic waves, vibrations, and lasers.
- the manufacturing apparatus of the microchip 2 is configured to manufacture the microchip 2 by forming the substrate 3 and the film 4 and then bonding them together. As shown in FIG. Etc.
- the molding apparatus 5 has a fixed side platen 51 and a movable side platen 52 on a base 50.
- the stationary side platen 51 is a flat plate-like member erected on the base 50.
- Columnar tie bars 53 are provided at the four corners of the fixed side platen 51 and extend perpendicular to the fixed side platen 51.
- the movable side platen 52 is a flat plate-like member disposed so as to face the fixed side platen 51, and is supported at four corners by tie bars 53 provided on the fixed side platen 51.
- the movable platen 52 is guided by a tie bar 53 and can be moved in a horizontal direction (in the directions of arrows A and Ab in the drawing), that is, in a contact / separation direction with the fixed platen 51 by a drive mechanism (not shown).
- a molding die 6 is disposed between the fixed platen 51 and the movable platen 52 described above.
- the molding die 6 is clamped, and the movable platen is moved.
- the mold 6 is opened when 52 moves in the direction of the arrow Ab.
- FIG. 8 is a cross-sectional view showing a schematic configuration of the mold 6 and shows a state in which the molding space is filled with resin.
- the molding die 6 is a molding die comprising a fixed die 60 as a first die and a movable die 61 as a second die provided so as to be able to contact and separate from the fixed die 60.
- the fixed mold 60 and the movable mold 61 are brought into contact with each other, so that a molding space 64 for molding the molten resin J into the shape of the substrate 3 is formed therebetween.
- the mold 6 is molded by injection molding. Specifically, a runner and a gate (not shown) are formed between the fixed mold 60 and the movable mold 61, and the molding resin 64 is filled into the molding space 64 through the runner and the gate. It is like that.
- the mold 6 may be molded by a molding method other than injection molding.
- the fixed mold 60 is for forming the inner surface 3 ⁇ / b> A (the surface on the film 4 side) of the substrate 3, and is fixed to the fixed platen 51.
- a fixed mold-molding surface 605 is formed as a molding surface of the inner side surface 3A.
- the fixed mold-forming surface 605 includes a protrusion 605A for forming the flow channel groove 30, and two columnar fixed mold-projections 605B for forming at least the first recess 32A of the positioning hole 32. Yes.
- the diameter of one positioning hole 32 when the diameter in the circumferential direction around the other positioning hole 32 is smaller than the diameter in the intersecting direction of the circumferential direction, the positioning hole In the fixed mold-projection portion 605B for molding 32, the diameter in the circumferential direction is made smaller than the diameter in the intersecting direction of the circumferential direction.
- FIG. 8 a state in which the central portion and the outer peripheral portion of the fixed mold 60 are configured by different members is illustrated, but it may be configured by a single member.
- the movable die 61 molds the outer side surface 3 ⁇ / b> B (surface opposite to the inner side surface 3 ⁇ / b> A) of the substrate 3, and is fixed to the movable side platen 52.
- the movable mold 61 is provided with a movable mold-molding surface 606 as a molding surface of the outer surface 3B.
- the movable mold-molding surface 606 has at least two columnar movable mold-projections 606B that mold the second recess 32B of the positioning hole 32 at a position opposed to the fixed mold-projection 605B.
- the movable mold-projection portion 606B is formed in a columnar shape having a larger diameter than the fixed mold-projection portion 605B, abuts against the tip of the fixed mold-projection portion 605B, and cooperates with the fixed mold-projection portion 605B.
- the positioning hole 32 is formed.
- the positioning hole In the movable mold-projection portion 606B for forming 32 when the diameter in the circumferential direction is smaller than the diameter in the intersecting direction of the circumferential direction, the positioning hole In the movable mold-projection portion 606B for forming 32, the diameter in the circumferential direction is made smaller than the diameter in the intersecting direction of the circumferential direction.
- the movable mold 61 is provided with an eject pin (not shown) that can be projected and retracted from the molding surface so that the molded product is released from the movable mold 61.
- FIG. 8 illustrates a state in which the central portion and the outer peripheral portion of the movable die 61 are configured by different members, but may be configured by a single member.
- the fixed mold 60 and the movable mold 61 as the central mold and the outer mold as described above, only the central mold having a fine structure such as a flow path can be replaced, and the cost of the entire mold can be reduced. There is an advantage that it becomes easy to cope with a change in the flow path configuration.
- the mold 6 as described above can be formed by electroforming or the like using a negative master (master mold) of the mold 6. In this case, it is possible to prevent the positional relationship between the channel groove 30 and the positioning hole 32 from changing every time the mold 6 is replaced.
- the molten resin J is injected into the molding space 64 through the runner and the gate, the molten resin J is molded while being pressurized in the molding space 64.
- the molten resin J is formed into the shape of the substrate 3, the flow path groove 30 is formed on the surface that becomes the inner surface 3 ⁇ / b> A, and the positioning hole portion 32 is formed penetrating in the thickness direction.
- the molded product is released from the fixed mold 60 by separating the movable mold 61 from the fixed mold 60.
- substrate 3 is manufactured by cutting the shaping
- the substrate 3 has the channel groove 30 formed in the inner side surface 3A, and the positioning hole 32 with respect to the channel groove 30 penetrates in the thickness direction.
- the fixed mold 60 that is formed and molds the inner surface 3A includes a protrusion 605A that molds the channel groove 30 and a columnar fixed mold-projection section that molds at least the minimum diameter portion 32C of the positioning hole 32.
- 605B, the minimum diameter portion 32C of the positioning hole 32, that is, the portion specified as the position of the positioning hole 32, and the flow channel groove 30 are formed by the same mold (fixed mold 60).
- the Rukoto The Rukoto.
- the positional relationship between the flow path groove 30 and the minimum diameter portion 32C of the positioning hole 32 can be kept constant between molding shots, based on the position of the minimum diameter portion 32C of the positioning hole 32, The position of the detection region 200 in the fine channel 20 can be accurately determined. Therefore, since there is no need to provide a conventional positioning channel, the position of the detection region 200 can be determined and the degree of freedom in designing the substrate 3 can be improved. In addition, since it is possible to save the trouble of performing the processing for determining the position of the detection region 200 such as focusing every time the measurement is performed, the control at the time of using the microchip 2 can be simplified and the inspection time can be shortened. .
- the position of the channel groove 30 can be determined more accurately.
- the movable die 61 is provided with a movable die-projection portion 606B that contacts the tip of the fixed die-projection portion 605B and forms the positioning hole 32 in cooperation with the fixed die-projection portion 605B. Therefore, the positioning hole 32 can be formed by being shared by the fixed mold-projection 605B and the movable mold-projection 606B. Therefore, compared with the case where the positioning hole 32 is formed with only one protrusion, the height of the protrusion can be reduced, so that the release property after forming can be improved.
- the movable mold-projection 606B is formed in a columnar shape having a larger diameter than the fixed mold-projection 605B, the corners of the movable mold-projection 606B and the fixed mold-projection 605B come into contact with each other and are damaged. Can be prevented.
- the fixed mold 60 is different from the case where the movable mold-projection portion 606B is provided in the fixed mold 60. It is possible to improve releasability from.
- the flow path groove 30 and the first concave portion 32A are formed on the inner side surface 3A by the fixed mold 60, it may be formed by the movable mold 61.
- FIG. 9 shows a state in which the positioning hole 32 is formed only by the fixed mold-projection 605B.
- the positioning hole 32 has been described as having the first concave portion 32A and the second concave portion 32B and penetrating through the substrate 3.
- the positioning hole portion 32 has only the first concave portion 32A and has a thickness direction from the inner side surface 3A. It is good also as being recessed.
- the molding die 6 is provided with only one of the fixed mold-projecting part 605B and the movable mold-projecting part 606B that molds the first recess 32A.
- the present invention is suitable for a microchip, a microchip mold, and a microchip manufacturing apparatus that can improve the degree of design freedom while allowing the position of the observation channel to be determined.
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- Manufacturing & Machinery (AREA)
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- Analytical Chemistry (AREA)
- Clinical Laboratory Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hematology (AREA)
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Abstract
Description
マイクロチップに具備される基板を成形するための成形型において、
前記基板は、
一方の面に流路用溝が形成されるとともに、当該溝に対する位置決め基準用の孔部が当該一方の面から厚み方向に形成されており、
前記一方の面にカバー部材が貼り合わされることで前記マイクロチップを形成するものであり、
当該成形型は、
第1型と、
前記第1型に対して接離可能に設けられた第2型と、を備え、
前記第1型及び前記第2型のうち、前記一方の面を成形する一方の型は、
前記溝を成形する突条と、
少なくとも前記孔部のうち、最も内径の小さくなる最小径部分を成形する柱状の第1突起部と、を有することを特徴とする。
基板とカバー部材とが貼り合わされたマイクロチップを製造するマイクロチップ製造装置において、
前記基板は、
一方の面に流路用溝が形成されるとともに、当該溝に対する位置決め基準用の孔部が厚み方向に貫通して形成されており、
当該基板の成形型として、
本発明の成形型を備えることを特徴とする。
基板とカバー部材とが貼り合わされたマイクロチップにおいて、
前記基板は、
成形によって形成されることで、
一方の面に流路用溝が形成されるとともに、当該溝に対する位置決め基準用の孔部が厚み方向に貫通して形成されており、
前記孔部は、
前記基板における前記一方の面から他方の面に向かって凹設された第1凹部と、
前記他方の面から前記一方の面に向かって凹設された第2凹部とが連通して形成されており、
前記第2凹部は、前記第1凹部よりも内径が大きいことを特徴とする。
最初に、本実施の形態における検査装置について、図1および図2を用いて説明する。
図1は検査装置1の外観構成の一例を示す斜視図であり、図2は検査装置1の内部構成の一例を示す模式図である。
送液部14は、マイクロチップ2内の送液を行うためのユニットであり、搬送口11から検査装置1内に搬入されるマイクロチップ2と接続されるようになっている。この送液部14は、マイクロポンプ140、チップ接続部141、駆動液タンク142および駆動液供給部143等を有している。
チップ接続部141は、マイクロポンプ140とマイクロチップ2とを接続して連通させる。
駆動液供給部143は、駆動液タンク142からマイクロポンプ140に駆動液146を供給する。
加熱部15は、マイクロチップ2を特定の複数の温度に加熱するために発熱する。例えば、約95℃の熱変性温度、約55℃のアニーリング温度、約70℃の重合温度の3つの温度にマイクロチップ2を加熱する。これにより、PCR法による遺伝子増幅を行う。加熱部15は、ヒータやペルチエ素子等の通電によって温度を上昇させられる素子、通水によって温度を低下させられる素子等で構成される。
電圧印加部18は、複数の電極を有している。これらの電極は、マイクロチップ2内の液体試料に挿入されて当該液体試料に直接電圧を印加するか、あるいは後述の通電部40に接触して当該通電部40を介して液体試料に電圧を印加することにより、マイクロチップ2内の液体試料に電気泳動を行わせるようになっている。
検出部16は、発光ダイオード(LED)やレーザ等の光源と、フォトダイオード(PD)等の受光部等とで構成され、マイクロチップ2内の反応によって得られる生成液に含まれる標的物質を、マイクロチップ2上の所定位置(後述の検出領域200)で光学的に検出する。光源と受光部との配置は透過型と反射型とがあり、必要に応じて決定されればよい。
駆動制御部17は、図示しないマイクロコンピュータやメモリ等で構成され、検査装置1内の各部の駆動、制御、検出等を行う。
続いて、本実施の形態におけるマイクロチップ2について、図3A,図3B,図3Cを用いて説明する。
図3A,図3B,図3Cは、マイクロチップ2を示す図であり、図3Aは平面図、図3B及び図3Cは側方から見た内部形状を示す透視図である。
この位置決め孔部32は、検査装置1に設けられた固定ピン(図示せず)を挿入されることでマイクロチップ2の位置、ひいては検出領域200の位置を所定位置に固定するものであり、基板3における2つの角部分において厚さ方向に貫通して設けられている。
続いて、マイクロチップ2の製造装置について説明する。
固定側プラテン51は、ベース50に立設された平板状の部材である。この固定側プラテン51の4隅には柱状のタイバー53が設けられており、固定側プラテン51に対して垂直に延在している。
図8は、成形型6の概略構成を示す断面図であり、成形空間に樹脂が充填された状態を示している。
この固定型60には、内側面3Aの成形面として固定型-成形面605が形成されている。
この可動型61には、外側面3Bの成形面として可動型-成形面606が形成されている。
続いて、以上の成形型6を用いた基板3の製造方法について説明する。
そして、ゲートによる成形部分を成形物からカットすることにより、基板3が製造される。
また、可動型-突起部606Bは固定型-突起部605Bよりも径の大きい柱状に形成されているので、可動型-突起部606Bと固定型-突起部605Bとの角部が当接して破損してしまうのを防止することができる。
3 基板
4 フィルム(カバー部材)
6 成形型
3A 内側面(一方の面)
3B 外側面(他方の面)
30 流路用溝
32 位置決め孔部(孔部)
32A 第1凹部
32B 第2凹部
60 固定型(第1型)
61 可動型(第2型)
605B 固定型-突起部(第1突起部)
606B 可動型-突起部(第2突起部)
Claims (9)
- マイクロチップに具備される基板を成形するための成形型において、
前記基板は、
一方の面に流路用溝が形成されるとともに、当該溝に対する位置決め基準用の孔部が当該一方の面から厚み方向に形成されており、
前記一方の面にカバー部材が貼り合わされることで前記マイクロチップを形成するものであり、
当該成形型は、
第1型と、
前記第1型に対して接離可能に設けられた第2型と、を備え、
前記第1型及び前記第2型のうち、前記一方の面を成形する一方の型は、
前記溝を成形する突条と、
少なくとも前記孔部のうち、最も内径の小さくなる最小径部分を成形する柱状の第1突起部と、を有することを特徴とする成形型。 - 請求項1記載の成形型において、
前記第1型及び前記第2型のうち、他方の型は、
前記第1突起部よりも径の大きい柱状に形成されて当該第1突起部の先端に当接し、この第1突起部と協働して前記孔部を前記基板内に貫通して成形する第2突起部を有することを特徴とする成形型。 - 請求項1または2記載の成形型において、
前記一方の型は、前記第1型であることを特徴とする成形型。 - 請求項2または3記載の成形型において、
前記第1突起部及び前記第2突起部をそれぞれ2つ有することを特徴とする成形型。 - 請求項4記載の成形型において、
2つの前記第1突起部のうち一方の第1突起部は、
当該第1突起部の長さ方向に垂直な断面内で、他方の第1突起部を中心とする円周方向の径が、当該円周方向の交差方向における径よりも小さくなり、かつ、前記他方の第1突起部の径と等しくなるよう形成されており、
2つの前記第2突起部のうち、前記一方の第1突起部に対応する一方の第2突起部は、
当該第2突起部の長さ方向に垂直な断面内で、他方の第2突起部を中心とする円周方向の径が、当該円周方向の交差方向における径よりも小さくなり、かつ、前記他方の第2突起部の径と等しくなるよう形成されていることを特徴とする成形型。 - 基板とカバー部材とが貼り合わされたマイクロチップを製造するマイクロチップ製造装置において、
前記基板は、
一方の面に流路用溝が形成されるとともに、当該溝に対する位置決め基準用の孔部が厚み方向に貫通して形成されており、
当該基板の成形型として、
請求項1~5の何れか一項に記載の成形型を備えることを特徴とするマイクロチップ製造装置。 - 基板とカバー部材とが貼り合わされたマイクロチップにおいて、
前記基板は、
成形によって形成されることで、
一方の面に流路用溝が形成されるとともに、当該溝に対する位置決め基準用の孔部が厚み方向に貫通して形成されており、
前記孔部は、
前記基板における前記一方の面から他方の面に向かって凹設された第1凹部と、
前記他方の面から前記一方の面に向かって凹設された第2凹部とが連通して形成されており、
前記第2凹部は、前記第1凹部よりも内径が大きいことを特徴とするマイクロチップ。 - 請求項7記載のマイクロチップにおいて、
前記孔部を2つ有することを特徴とするマイクロチップ。 - 請求項8記載のマイクロチップにおいて、
前記2つの孔部のうち、一方の孔部は、
当該孔部の深さ方向に垂直な断面内で、他方の孔部を中心とする円周方向の径が、当該円周方向の交差方向における径よりも小さくなり、かつ、前記他方の孔部の径と等しくなるよう形成されていることを特徴とするマイクロチップ。
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13/882,352 US9238322B2 (en) | 2010-10-29 | 2011-10-25 | Microchip, molding die for microchip, and manufacturing apparatus for manufacturing microchip |
| JP2012540856A JP5768228B2 (ja) | 2010-10-29 | 2011-10-25 | マイクロチップ、マイクロチップの成形型、及びマイクロチップを製造する製造装置 |
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| JP2010-243639 | 2010-10-29 | ||
| JP2010243639 | 2010-10-29 |
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| PCT/JP2011/074478 Ceased WO2012057101A1 (ja) | 2010-10-29 | 2011-10-25 | マイクロチップ、マイクロチップの成形型、及びマイクロチップを製造する製造装置 |
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| US (1) | US9238322B2 (ja) |
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| JP2014206482A (ja) * | 2013-04-15 | 2014-10-30 | 株式会社島津製作所 | 光または放射線測定用容器並びに測定システム |
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| JP6854206B2 (ja) * | 2017-07-12 | 2021-04-07 | アルプスアルパイン株式会社 | 流路チップ及び流路チップの位置決め方法 |
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| JP2000310615A (ja) * | 1999-02-26 | 2000-11-07 | Hitachi Chem Co Ltd | 電気泳動用チップとその製造方法、該電気泳動用チップを用いた電気泳動装置及び荷電性物質の分離方法 |
| JP2008224431A (ja) * | 2007-03-13 | 2008-09-25 | Konica Minolta Opto Inc | マイクロチップの製造方法、及びマイクロチップ |
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| WO2010110014A1 (ja) * | 2009-03-27 | 2010-09-30 | コニカミノルタオプト株式会社 | 射出成形用金型、射出成形方法及び射出成形品 |
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|---|---|---|---|---|
| US4579709A (en) * | 1983-11-23 | 1986-04-01 | Nicholas Ferrari | Method for molding hinged article |
| JP3312598B2 (ja) | 1998-08-19 | 2002-08-12 | 株式会社島津製作所 | マイクロチップ電気泳動装置 |
| WO2008087800A1 (ja) * | 2007-01-17 | 2008-07-24 | Konica Minolta Opto, Inc. | マイクロチップの製造方法、及びマイクロチップ |
| US7967348B2 (en) * | 2007-10-10 | 2011-06-28 | Honeywell International Inc. | Key alignment system for keyed safety interlocks |
| JP2009166416A (ja) * | 2008-01-18 | 2009-07-30 | Konica Minolta Opto Inc | マイクロチップの製造方法、及びマイクロチップ |
-
2011
- 2011-10-25 US US13/882,352 patent/US9238322B2/en not_active Expired - Fee Related
- 2011-10-25 JP JP2012540856A patent/JP5768228B2/ja not_active Expired - Fee Related
- 2011-10-25 WO PCT/JP2011/074478 patent/WO2012057101A1/ja not_active Ceased
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2000310615A (ja) * | 1999-02-26 | 2000-11-07 | Hitachi Chem Co Ltd | 電気泳動用チップとその製造方法、該電気泳動用チップを用いた電気泳動装置及び荷電性物質の分離方法 |
| JP2008224431A (ja) * | 2007-03-13 | 2008-09-25 | Konica Minolta Opto Inc | マイクロチップの製造方法、及びマイクロチップ |
| WO2009034819A1 (ja) * | 2007-09-11 | 2009-03-19 | Konica Minolta Medical & Graphic, Inc. | マイクロチップの製造方法、マイクロチップ、真空貼付装置 |
| WO2010110014A1 (ja) * | 2009-03-27 | 2010-09-30 | コニカミノルタオプト株式会社 | 射出成形用金型、射出成形方法及び射出成形品 |
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| JP2014206482A (ja) * | 2013-04-15 | 2014-10-30 | 株式会社島津製作所 | 光または放射線測定用容器並びに測定システム |
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| Publication number | Publication date |
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| US20130209733A1 (en) | 2013-08-15 |
| JP5768228B2 (ja) | 2015-08-26 |
| JPWO2012057101A1 (ja) | 2014-05-12 |
| US9238322B2 (en) | 2016-01-19 |
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